Overall 5-year survival in children with acute lymphoblastic leukemia improved from 83.7% to 90.4% between the early 1990s and the early 2000s, according to a report published online March 12 in the Journal of Clinical Oncology.
Five-year survival improved by 30%-50% across all subgroups of patients during this interval, with one discouraging exception: It remained steady and much lower in infants aged less than 1 year, said Dr. Stephen P. Hunger of the University of Colorado Cancer Center and his associates in the Children’s Oncology Group (COG).
The investigators assessed outcomes in 21,626 children and adolescents participating in 36 ALL clinical trials in 1990-2005, which they described as "the largest childhood ALL cohort ever reported." The COG includes more than 200 member institutions in the United States, Canada, and other countries, which together have enrolled 56% of all cases of pediatric ALL that occurred in the United States between 1990 and 2005 in clinical trials.
"Thus, our results are representative of survival following contemporary therapy in the U.S." and differ somewhat from those of other large groups such as the National Cancer Institute’s SEER program, they said.
Dr. Hunger and his colleagues divided this cohort into three similar-sized groups in three eras: 7,304 patients treated in 1990-1994; 7,169 treated in 1995-1999; and 7,153 treated in 2000-2005. The median follow-up was 9.13 years, 8.02 years, and 5.35 years, respectively.
Most (92%) of these study subjects were treated in the United States, with 6% treated in Canada and 2% treated elsewhere.
Overall 5-year survival increased from 83.7% in the first era to 87.7% in the second and to 90.4% in the third. "We believe that the major reason for improved survival was decreased risk of relapse," they said (J. Clin. Oncol. 2012 March 12 [doi:10.1200/JCO.20911.37.8018]).
This is because the rate of deaths from relapse decreased markedly during this interval, from 43% in 1990-1994 to 27% in 2000-2005.
Among infants, the 5-year risk of death changed little, at 52.1% in 1990-1994 and 50.3% in 2000-2005. During the study period, "the COG pursued several strategies to attempt to increase survival for infants with ALL. Chemotherapy treatment was intensified significantly" in two clinical trials, while stem-cell transplantation was explored in others.
Stem-cell therapy was not found to be beneficial in infants in these studies, and chemotherapy intensification raised the rate of treatment-related death to the same degree that it lowered the rate of death from disease progression, with no net improvement in survival.
"Infant ALL is a unique high-risk subset that requires new therapeutic strategies," the researchers said.
Five-year survival improved 30%-50% across all other subgroups of patients: in all age groups (except infants), in both sexes, in all races and ethnicities, in patients with B-cell or T-cell disease, in patients with average-risk or high-risk profiles, and across all features of ALL according to NCI criteria.
However, the risk of death still remained higher in patients aged 10 or older, compared with those aged 1-10, higher in boys than in girls, higher in blacks and Hispanics than in whites, and higher in T-cell than in B-cell disease. Risk of death was two- to fourfold higher in patients high-risk than in average-risk patients.
It was encouraging that the "racial gap" in outcomes between whites and nonwhites narrowed during the study period. For example, the absolute difference in 5-year survival between whites and blacks declined from 11.0% in 1990-1994 to only 3.3% in 2000-2005. Racial differences between whites and nonwhites in ALL biology are still evident, with black and Hispanic patients being more likely than whites to carry higher-risk forms of the disease or higher-risk genetic profiles, the investigators noted.
A total of 36% of the ALL deaths in these study subjects occurred in patients who were at average risk. "Thus, efforts to decrease ALL deaths must focus both on high-risk patient subsets and on the large subset of patients with favorable clinical characteristics," Dr. Hunger and his associates said.
Based on their data, the researchers also "anticipate significant improvements in 10-year survival."
Children’s Oncology Group studies are supported by the National Cancer Institute. Dr. Hunger reported no financial conflicts of interest. One associate reported ties to EUSA Pharma, Sanofi-Aventis, Teva Pharmaceutical Industries, Bristol-Myers Squibb, Enzon Pharmaceuticals, Sigma Tau Pharmaceuticals, and Genzyme.